A Fluorinated BODIPY-Based Zirconium Metal-Organic Framework for In Vivo Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), an emergent noninvasive cancer treatment, is largely dependent on the presence of efficient photosensitizers (PSs) and a sufficient oxygen supply. However, the therapeutic efficacy of PSs is greatly compromised by poor solubility, aggregation tendency, and oxygen depletion within solid tumors during PDT in hypoxic microenvironments. Despite the potential of PS-based metal-organic frameworks (MOFs), addressing hypoxia remains challenging. Boron dipyrromethene (BODIPY) chromophores, with excellent photostability, have exhibited great potential in PDT and bioimaging. However, their practical application suffers from limited chemical stability under harsh MOF synthesis conditions. Herein, we report the synthesis of the first example of a Zr-based MOF, namely, 69-L2, exclusively constructed from the BODIPY-derived ligands via a single-crystal to single-crystal post-synthetic exchange, where a direct solvothermal method is not applicable. To increase the PDT performance in hypoxia, we modify 69-L2 with fluorinated phosphate-functionalized methoxy poly(ethylene glycol). The resulting 69-L2@F is an oxygen carrier, enabling tumor oxygenation and simultaneously acting as a PS for reactive oxygen species (ROS) generation under LED irradiation. We demonstrate that 69-L2@F has an enhanced PDT effect in triple-negative breast cancer MDA-MB-231 cells under both normoxia and hypoxia. Following positive results, we evaluated the in vivo activity of 69-L2@F with a hydrogel, enabling local therapy in a triple-negative breast cancer mice model and achieving exceptional antitumor efficacy in only 2 days. We envision BODIPY-based Zr-MOFs to provide a solution for hypoxia relief and maximize efficacy during in vivo PDT, offering new insights into the design of promising MOF-based PSs for hypoxic tumors.

Effect of incisal preparation design on the fracture strength of monolithic zirconia-reinforced lithium silicate laminate veneers.

PURPOSE: This study aimed to assess the fracture resistance of monolithic zirconia-reinforced lithium silicate laminate veneers (LVs) fabricated on various incisal preparation designs. MATERIALS AND METHODS: Sixty maxillary central incisors with various preparation designs were 3D-printed, 15 each, including preparation for: (1) LV with feathered-edge design; (2) LV with butt-joint design; (3) LV with palatal chamfer; and (4) full-coverage crown. Restorations were then designed and manufactured from zirconia-reinforced lithium silicate (ZLS) following the contour of a pre-operation scan. Restorations were bonded to the assigned preparation using resin cement and following the manufacturer's instructions. Specimens were then subjected to 10,000 thermocycles at 5 to 55°C with a dwell time of 30 s. The fracture strength of specimens was then assessed using a universal testing machine at a crosshead speed of 1.0 mm/min. One-way ANOVA and Bonferroni correction multiple comparisons were used to assess the fracture strength differences between the test groups (α = 0.001). Descriptive fractographic analysis of specimens was carried out with scanning electron microscopy images. RESULTS: Complete coverage crown and LV with palatal chamfer design had the highest fracture resistance values (781.4 ± 151.4 and 618.2 ± 112.6 N, respectively). Single crown and LV with palatal chamfer had no significant difference in fracture strength (p > 05). LV with feathered-edge and butt-joint designs provided significantly (p < 05) lower fracture resistance than complete coverage crown and LV with palatal chamfer design. CONCLUSION: The fracture resistance of chairside milled ZLS veneers was significantly influenced by the incisal preparation designs tested. Within the limitation of this study, when excessive occlusal forces are expected, LV with palatal chamfer display is the most conservative method of fabricating an indirect restoration.

Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma.

Bispecific T cell engagers (TCEs) are an emerging anti-cancer modality that redirects cytotoxic T cells to tumor cells expressing tumor-associated antigens (TAAs), thereby forming immune synapses to exert anti-tumor effects. Designing pharmacokinetically acceptable TCEs and optimizing their size presents a considerable protein engineering challenge, particularly given the complexity of intercellular bridging between T cells and tumor cells. Therefore, a physiologically-relevant and clinically-verified computational modeling framework is of crucial importance to understand the protein engineering trade-offs. In this study, we developed a quantitative, physiologically-based computational framework to predict immune synapse formation for a variety of molecular formats of TCEs in tumor tissues. Our model incorporates a molecular size-dependent biodistribution using the two-pore theory, extravasation of T cells and hematologic cancer cells, mechanistic bispecific intercellular binding of TCEs, and competitive inhibitory interactions by shed targets. The biodistribution of TCEs was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. Parameter sensitivity analyses indicated that immune synapse formation was highly sensitive to TAA expression, degree of target shedding, and binding selectivity to tumor cell surface TAAs over shed targets. Notably, the model suggested a "sweet spot" for TCEs' CD3 binding affinity, which balanced the trapping of TCEs in T-cell-rich organs. The final model simulations indicated that the number of immune synapses is similar (~55/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in an IgG format and AMG420 in a BiTE format, at their respective efficacious doses in multiple myeloma patients. This result demonstrates the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs, thus suggesting that this framework can be applied to other targets to provide a quantitative means to facilitate model-informed best-in-class TCE discovery and development.

Zirconia-veneered polyetherketoneketone frameworks of implant-supported complete arch fixed dental prostheses: A report on 5 patients.

Metal frameworks have been used for implant-supported complete arch fixed dental prostheses (ISCFDPs) for maxillary or mandibular edentulous arches with a crown height space of more than 15 mm. However, technical difficulties in the casting, weight, and lack of passivity of the metal have led dentists and dental laboratory technicians to choose materials with different biomechanical properties, including polyetheretherketone (PEEK) and polyetherketoneketone (PEKK). This clinical report describes the design of ISCFDPs using PEKK frameworks, the number of cantilevers, the condition of the opposing dentition, and the incidence of complications, including zirconia crown or PEKK framework fracture, as well as the clinical outcomes of 5 patients observed prospectively over 8 to 65 months. No mechanical complications of PEKK-made ISCFDPs opposing removable prostheses occurred, regardless of the presence of cantilevers. The ISCFDPs that opposed natural dentition or a combination of the natural dentition and fixed prostheses showed different clinical outcomes depending on the length of cantilevers and the number and location of pontics.

An in vitro trial on the effect of arch form on connector size requirements in long span anterior zirconia fixed dental prostheses.

PURPOSE: To test the fracture resistance of maxillary canine to canine fixed partial denture with four missing incisors, with increasing anterior-cantilevers of the pontics and varying connector sizes. MATERIALS AND METHODS: Two 3D-printed titanium alloy (Ti6Al4V) models mimicking a maxillary canine to canine fixed partial denture (FPD) with four pontics replacing the incisors were used as master models. Zirconia FPDs were digitally designed and milled with two different connector sizes (9 and 12 mm2 ) each with three different anterior cantilevers (7, 10, and 13 mm) accounting for 6 test groups. Seven samples were milled for each group generating a total of 42 samples. The zirconia FPDs were cemented on the titanium model using resin modified glass ionomer cement and the model fixated to a variable angle vice. A sinusoidal cyclic waveform load from 50 to 280N was applied using a universal testing machine at a frequency of 30 cycles per second and a total of 5 million cycles. RESULTS: The results of Fisher's exact tests showed that the difference in the proportion of fractured versus nonfractured fixed partial dentures was not statistically significant when comparing the 9 with the 12 mm2 connector size (p = 1.00), as well as when comparing the six test groups (p = 0.2338); on the other hand, it proved to be statistically significant when comparing the 7 mm cantilever with the 10 and 13 mm cantilevers combined (p = 0.0407) indicating that a 7 mm anterior spread of the pontics showed a significantly greater proportion of fixed partial dentures that fractured. CONCLUSIONS: Fracture susceptibility was not a function of cantilever length in this testing configuration for anterior FPDs. Retainer crown thickness seems to be a more important parameter than connector size thickness. Based on the results, a smaller connector size (9 mm2 ) can be used to improve the esthetics of pontics in long span anterior FPDs.

Different Designs of Deep Marginal Elevation and Its Influence on Fracture Resistance of Teeth with Monolith Zirconia Full-Contour Crowns.

Background and objectives: Even with the demand for high esthetics, the strength of the material for esthetic applications continues to be important. In this study, monolith zirconia (MZi) crowns fabricated using CAD/CAM were tested for fracture resistance (FR) in teeth with class II cavity designs with varying proximal depths, restored through a deep marginal elevation technique (DME). Materials and Methods: Forty premolars were randomly divided into four groups of ten teeth. In Group A, tooth preparation was conducted and MZi crowns were fabricated. In Group B, mesio-occluso-distal (MOD) cavities were prepared and restored with microhybrid composites before tooth preparation and the fabrication of MZi crowns. In Groups C and D, MOD cavities were prepared, differentiated by the depth of the gingival seat, 2 mm and 4 mm below the cemento-enamel junction (CEJ). Microhybrid composite resin was used for DME on the CEJ and for the restoration of the MOD cavities; beforehand, tooth preparations were conducted and MZi crowns were and cemented using resin cement. The maximum load to fracture (in newtons (N)) and FR (in megapascals (MPa)) were measured using the universal testing machine. Results: The average scores indicate a gradual decrease in the load required to fracture the samples from Groups A to D, with mean values of 3415.61 N, 2494.11 N, 2108.25 N and 1891.95 N, respectively. ANOVA revealed highly significant differences between the groups. Multiple group comparisons using the Tukey HSD post hoc test revealed that Group D had greater DME depths and showed significant differences compared with Group B. Conclusions: FR in teeth decreased when more tooth structure was involved, even with MZi crowns. However, DME up to 2 mm below the CEJ did not negatively influence the FR. Strengthening the DME-treated teeth with MZi crowns could be a reasonable clinical option, as the force required to fracture the samples far exceeded the maximum recorded biting force for posterior teeth.

Zirconium cyclosilicate: An oral sorbent for potassium, four decades in the making.

HemoCleanse collaborated with Dr. John Sherman and Union Carbide in the 1980s to develop a cation exchanger with high selectivity for potassium and ammonium, for use in a wearable artificial kidney. Synthetic zeolites had unexpected solubility in this application but by 2000, UOP (a sister company of Union Carbide) had developed zirconium cyclosilicate (SZC). HemoCleanse performed early animal studies of SZC as an oral sorbent. These showed remarkable binding characteristics. HemoCleanse then obtained the license for SZC for medical applications, helped to form ZS Pharma, and collaborated in further animal studies and clinical trials. AstraZeneca purchased ZS Pharma in 2015, and SZC (Lokelma®) has now become an effective treatment for hyperkalemia in patients with kidney failure and cardiac conditions.

Fabrication of an implant-retained overdenture with ceramic crowns cemented on a polyetherketoneketone framework: A clinical report.

This clinical report describes the treatment of a complex intraoral situation by fabricating a maxillary implant-retained overdenture with a high-performance polymer (polyetherketoneketone) framework and lithium disilicate crowns and mandibular tooth- and implant-supported ceramic restorations. No complications were noted in 2 years, and the patient was satisfied with function and esthetics.

Clinical evaluation of monolithic zirconia multiunit posterior fixed dental prostheses.

STATEMENT OF PROBLEM: Monolithic zirconia restorations have been evaluated with in vitro studies, but limited clinical evidence of their longevity and reliability is available. PURPOSE: The purpose of this clinical study was to evaluate the clinical performance of posterior multiunit glazed monolithic zirconia fixed dental prostheses. MATERIAL AND METHODS: A total of 20 participants received 33 monolithic posterior zirconia fixed dental prostheses (Zolid white; Amann Girrbach AG) with minimally invasive preparations. Bilaterally supported fixed dental prostheses with a connector area of at least 9 mm2 were luted with resin-modified glass ionomer cement. The clinical evaluations were performed after 1 week, 6 months, and then annually after completion of the treatment. The biologic outcomes were evaluated by assessing the pocket depth, attachment level, plaque control, bleeding on probing, caries, and tooth vitality. Esthetics and the functional performance of the prostheses (color match, cavosurface marginal discoloration, anatomic form, marginal adaptation) were evaluated as per the rating scales of Cvar and Ryge. An analysis of survival was made by using the Kaplan-Meier method. RESULTS: After 39.8 ±16.7 months of observation, the overall survival rate of the monolithic zirconia multiunit posterior prostheses was 93.9%. No caries were found on the abutment teeth, signs of gingivitis were noted in 1 participant after 24 months, and increased probing depths of the abutment teeth were detected in 5 prostheses (15.1%). No loss of retention was detected. Two prostheses had to be replaced: 1 because of a biologic complication and 1 because of a technical complication. The remaining 31 prostheses received Alfa scores for marginal adaptation, cavosurface marginal discoloration, and caries. Twenty-seven (87.1%) prostheses were rated as Alfa and 4 (12.9%) as Bravo for anatomic form. The color match was noted as Alfa in 15 (48.3%) prostheses, and 16 (51.6%) were rated as Bravo. CONCLUSIONS: Monolithic zirconia restorations demonstrated a reliable treatment option after medium-term clinical use for the replacement of missing posterior teeth.

Clinical outcomes of veneered zirconia anterior partial fixed dental prostheses: A 12-year prospective clinical trial.

STATEMENT OF PROBLEM: Anterior veneered zirconia partial fixed dental prostheses (FDPs) have substituted for metal-ceramic to improve esthetics and biocompatibility. However, the material is susceptible to aging or hydrothermal degradation and to chipping of the feldspathic veneer. Whether these susceptibilities limit the clinical performance of anterior veneered zirconia FPDs is unclear. PURPOSE: The purpose of this prospective clinical study was to analyze the mechanical and biologic behavior of zirconia partial FDPs in the anterior region over a 12-year follow-up period. MATERIAL AND METHODS: Twenty-seven 3- to 6-unit FDPs fabricated from zirconia veneered with feldspathic porcelain were placed in the anterior region and examined clinically at 1 month, 6 months, and then annually for 12 years, recording mechanical and biologic outcomes. Raw complication rates and time-to-event Kaplan-Meier analysis was conducted and compared as per the partial fixed dental prosthesis type. RESULTS: Five FDPs had biologic complications (3 with secondary caries, 1 with periapical pathology, 1 with periodontal disease) and 9 had mechanical complications (7 with chipping and 2 with decementation). Chipping was the most prevalent complication and increasingly found with longer-span fixed partial prostheses (P=.007). Five FDPs had to be replaced because of complete failure, the most frequent cause of failure being secondary caries (P=.003). The mean survival rate (no failures) was 11 years 4 months (95% confidence interval, 10.3-12.7). CONCLUSIONS: Zirconia FDPs had an 81.5% survival rate over 12 years. A higher incidence of complications took place during the first 3 years, the most common being chipping.

Fracture load of zirconia crowns based on preparation and cement type.

Limited research has been published evaluating the failure of zirconia crowns with less retentive tooth preparations. The purpose of this study was to evaluate the effect of axial wall height (AWH) and cement type on the fracture load of cubic phase-containing zirconia crowns. Standardized crown preparations with an AWH of 0, 2, or 4 mm (n = 10) were made in 90 extracted human maxillary third molars. The preparations were scanned, and crown restorations were designed. Cubic phase-containing zirconia crowns were milled and cemented with a resin-modified glass ionomer cement, a self-adhesive resin cement, or an adhesive resin cement. The specimens were subjected to thermocycling and cyclic loading. Each crown specimen was positioned in a universal testing machine so that the long axis of the tooth was at a 60° angle to the testing fixture and loaded until failure using a stainless steel rod resting on the buccal incline of the palatal cusp. Data were found to have a nonnormal distribution and were analyzed with Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Statistically significant differences in the median fracture loads of the groups were found based on both AWH and cement type (P < 0.05). Regardless of cement type, the median fracture loads were significantly lower in the 0-mm AWH groups than in the 2-mm and 4-mm AWH groups, which were not significantly different from each other. Compared to the other cement types, adhesive resin cement resulted in a significantly greater median fracture load when the AWH was 0 mm. The use of an adhesive resin cement with a cubic phase-containing zirconia crown may provide greater fracture resistance for preparations with minimal AWH.

Are zirconia crowns the superior choice when restoring primary posterior molars?

Data sources Electronic database searches were carried out using predefined search terms using Embase, Google Scholar, Medline, The Cochrane Library, The Cochrane Central Register of Controlled Trials and Latin American and Caribbean Health Sciences Literature. The Trip medical database was also used to identify randomised control trials investigating stainless steel and zirconia crowns. Studies published from 1 January 2000 until 6 June 2021 were included, and reference lists of included studies analysed to ensure data saturation along with grey literature searches.Study selection Inclusion criteria included research published in English only, randomised control trials investigating the clinical and radiographic effectiveness of zirconia crowns compared to stainless steel crowns, the rehabilitation of pulp-treated posterior primary teeth and randomised control trials with children in good health. Expert opinion, case reports and reviews were excluded. Studies with a follow-up period of less than 12 months, studies including children with special care requirements or non-compliant children were also excluded.Data extraction and synthesis Two reviewers (AKP, VKC) were involved with the primary search of abstracts and titles independently; both reviewers were involved in full text assessment. Disagreements were resolved by a third reviewer (NRV). The study characteristics, number of teeth evaluated, follow-up duration, type of zirconia and stainless steel crowns, outcome assessed and outcome results were extracted. Extracted data was analysed using Review Manager, Version 5.3 and dichotomous data was summarised as risk ratios with 95% confidence intervals. Continuous data was summarised as mean difference. Heterogeneity was summarised by I2 scores and a random-effects model and Mantel-Haenszel statistical test was used.Results From the initial 641 studies screened, six studies met the inclusion criteria for the systematic review and were included for analysis. Risk of bias assessment for the included studies was graded as 'low' for three of the six included studies and 'some concern' for the remaining three studies. This was based upon allocation concealment in the randomised control trials. Clinical failures were observed in 63 of 497 events. Rehabilitation with zirconia crowns may result in less clinical failures than stainless steel crowns: risk ratio 0.48; 95% CI (0.15-1.52) p = 0.021. Gingival health was better with zirconia rather than stainless steel crowns: risk ratio 0.32; 95% CI (-0.42-0.23) p <0.001.Conclusions Primary posterior teeth restored with zirconia crowns may have 52% less risk of experiencing clinical failures than teeth with stainless steel crowns and better gingival health than stainless steel crowns, observed after 12 months. However, due to the low quality of included studies and 'very low' grade rating of the evidence provided, further clinical trials are required to provide further evidence on the clinical and radiographic effectiveness of zirconia and stainless steel crowns.

Effectiveness of Nanohydroxyapatite on Demineralization of Enamel and Cementum Surrounding Margin of Yttria-Stabilized Zirconia Polycrystalline Ceramic Restoration.

INTRODUCTION: Prosthetic dentistry has shifted toward prevention of caries occurrence surrounding restorative margin through the anti-demineralization process. This study examines the ability of nanohydroxyapatite (NHA) gel and Clinpro (CP) on enhancing resistance to demineralization of enamel and cementum at margin of restoration. MATERIALS AND METHODS: Thirty extracted mandibular third molars were segregated at 1 mm above and below cementoenamel junction (CEJ) to separate CEJ portions and substituted with zirconia disks by bonding to crown and root portions with resin adhesive. The enamel and cementum area of 4 × 4 mm2 neighboring zirconia was applied with either NHA or CP, while one group was left no treatment (NT) before demineralized with carbopal. Vickers hardness (VHN) of enamel and cementum was evaluated before material application (B M), after material application (A M), and after demineralization (A D). Analysis of variance (ANOVA) and post hoc multiple comparisons were used to justify for the significant difference (α = 0.05). Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were determined for surface evaluations. RESULTS: The mean ± SD of VHN for B M, A M, and A D for enamel and cementum was 393.24 ± 26.27, 392.89 ± 17.22, 155.00 ± 5.68 and 69.89 ± 4.59, 66.28 ± 3.61, 18.13 ± 0.54 for NT groups, respectively, 390.10 ± 17.69, 406.77 ± 12.86, 181.55 ± 7.99 and 56.01 ± 9.26, 62.71 ± 6.15, 19.09 ± 1.16 for NHA groups, respectively, and 387.90 ± 18.07, 405.91 ± 9.83, 188.95 ± 7.43 and 54.68 ± 7.30, 61.81 ± 4.30, 19.22 ± 1.25 for CP groups, respectively. ANOVA indicated a significant increase in anti-demineralization of enamel and cementum upon application of NHA or CP (p < 0.05). Multiple comparisons indicated the capability in inducing surface strengthening to resist demineralization for enamel and cementum of NHA which was comparable to CP (p > 0.05) as evidenced by SEM and XRD data indicating NHA and CP deposition and crystallinity accumulation. CONCLUSION: NHA and CP were capable of enhancing anti-demineralization for enamel and cementum. The capability in resisting the demineralization process of NHA was comparable with CP. NHA was highly recommended for anti-demineralization for enamel and cementum surrounding restorative margin.

Bacteriological Evaluation of Gingival Crevicular Fluid in Teeth Restored Using Fixed Dental Prostheses: An In Vivo Study.

The present in vivo study determined the microbiological counts of the gingival crevicular fluid (GCF) among patients with fixed dental prostheses fabricated using three different techniques. A total of 129 subjects were divided into three study groups: first, cobalt-chrome-based, metal-ceramic prostheses fabricated by the conventional method (MC, n = 35); the second group consisted of cobalt-chrome-based, metal-ceramic prostheses fabricated by the computer-aided design and computer-aided manufacturing (CAD/CAM) technique (CC-MC, n = 35); the third group comprised zirconia-based ceramic prostheses fabricated using the CAD/CAM technique (CC-Zr, n = 35). The control consisted of 24 patients using prostheses fabricated with either MC, CC-MC, or CC-Zr. The GCF was obtained from the subjects before treatment, and 6 and 12 months after the prosthetic treatment. Bacteriological and bacterioscopic analysis of the GCF was performed to analyze the patients' GCF. The data were analyzed using SPSS V20 (IBM Company, Chicago, IL, USA). The number of microorganisms of the gingival crevicular fluid in all groups at 12 months of prosthetic treatment reduced dramatically compared with the data obtained before prosthetic treatment. Inflammatory processes in the periodontium occurred slowly in the case of zirconium oxide-based ceramic constructions due to their biocompatibility with the mucous membranes and tissues of the oral cavity as well as a reduced risk of dental biofilm formation. This should be considered by dentists and prosthodontists when choosing restoration materials for subjects with periodontal pathology.

Hydroxypyridinones as a Very Promising Platform for Targeted Diagnostic and Therapeutic Radiopharmaceuticals.

Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals.

Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted 89Zr-Pertuzumab PET/CT.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies are successful in patients with HER2-positive malignancies; however, spatial and temporal heterogeneity of HER2 expression may prevent identification of optimal patients for these therapies. Purpose To determine whether imaging with the HER2-targeted PET tracer zirconium 89 (89Zr)-pertuzumab can depict HER2-positive metastases in women with HER2-negative primary breast cancer. Materials and Methods From January to June 2019, women with biopsy-proven HER2-negative primary breast cancer and biopsy-proven metastatic disease were enrolled in a prospective clinical trial (ClinicalTrials.gov NCT02286843) and underwent 89Zr-pertuzumab PET/CT for noninvasive whole-biopsy evaluation of potential HER2-positive metastases. 89Zr-pertuzumab-avid foci that were suspicious for HER2-positive metastases were tissue sampled and examined by pathologic analysis to document HER2 status. Results Twenty-four women (mean age, 55 years ± 11 [standard deviation]) with HER2-negative primary breast cancer were enrolled. Six women demonstrated foci at 89Zr-pertuzumab PET/CT that were suspicious for HER2-positive disease. Of these six women, three had biopsy-proven HER2-positive metastases, two had pathologic findings that demonstrated HER2-negative disease, and one had a fine-needle aspirate with inconclusive results. Conclusion Human epidermal growth factor receptor 2 (HER2)-targeted imaging with zirconium 89-pertuzumab PET/CT was successful in detecting HER2-positive metastases in women with HER2-negative primary breast cancer. This demonstrates the ability of targeted imaging to identify patients for targeted therapies that might not otherwise be considered. © RSNA, 2020 Online supplemental material is available for this article. See the editorial by Mankoff and Pantel in this issue.

Dual-Functional Supernanoparticles with Microwave Dynamic Therapy and Microwave Thermal Therapy.

The cytotoxic reactive oxygen species (ROS) generated by photoactivated sensitizers have been well explored in tumor therapy for nearly half a century, which is known as photodynamic therapy (PDT). The poor light penetration depth severely hinders PDT as a primary or adjuvant therapy for clinical indication. Whereas microwaves (MWs) are advantageous for deep penetration depth, the MW energy is considerably lower than that required for the activation of any species to induce ROS generation. Herein we find that liquid metal (LM) supernanoparticles activated by MW irradiation can generate ROS, such as ·OH and ·O2. On this basis, we design dual-functional supernanoparticles by loading LMs and an MW heating sensitizer ionic liquid (IL) into mesoporous ZrO2 nanoparticles, which can be activated by MW as the sole energy source for dynamic and thermal therapy concomitantly. The microwave sensitizer opens the door to an entirely novel dynamic treatment for tumors.

Bulking for stress urinary incontinence in men: A systematic review.

AIMS: An updated literature review on outcomes in men treated with currently commercially available bulking agents was performed to determine whether this is a reasonable option in selected patients. METHODS: The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework of systematic reviews. A comprehensive search of PubMed, Medline, and Embase was undertaken. Abstracts were independently screened by two investigators to include men with stress urinary incontinence treated with a peri-urethral injection of bulking agents currently available in the market. RESULTS: Only eight original articles met the inclusion criteria. The bulking agents used were Macroplastique in five studies (total 123 patients), Opsys, Durasphere, and Urolastic in one study each (10, 7, and 2 patients, respectively). Only one study was randomized; Macroplastique vs AUS in men with mild or total incontinence. The included populations were heterogeneous and encompassed endoscopic, perineal, abdominal and laparoscopic prostate surgery as well as spinal cord injuries and urethral sphincter insufficiency. Significant dissimilarity was evident for the duration of incontinence (9-108 months), mean volume of bulking agent used (2.3-13.5 mL), number of cushions (1-5), depth and position of the cushions. The outcomes varied significantly, with reported dry rates between 0% and 83%. Outcomes were limited by relatively short follow-up in most studies. CONCLUSION: Following initial enthusiasm and then dismay with collagen-based compounds, sparse and heterogeneous literature data were produced on newer non-migrating and nonabsorbable bulking agents. Some studies have suggested encouraging, if short term outcomes, however, future studies are needed in this field to support recommendations for widespread use.

Cerebral rituximab uptake in multiple sclerosis: A 89Zr-immunoPET pilot study.

Previous studies have demonstrated that the chimeric monoclonal antibody rituximab significantly reduces clinical and radiological disease activity in relapsing-remitting multiple sclerosis as early as 4 weeks after the first administration. The exact mechanisms leading to this rapid effect have not yet been clarified. The aim of this positron emission tomography study was to assess central nervous system penetration as a possible explanation, using zirconium-89-labelled rituximab. No evidence was found for cerebral penetration of [89Zr]rituximab.

Early histological, microbiological, radiological, and clinical response to cemented and screw-retained all-ceramic single crowns.

OBJECTIVES: To assess the early histological, microbiological, radiological, and clinical response to cemented and screw-retained all-ceramic single-tooth implant-supported reconstructions. MATERIALS AND METHODS: Patients with single-tooth implants were randomly allocated to receive a cemented lithium disilicate crown on a customized zirconia abutment (CEM) or a screw-retained crown with a directly veneered zirconia abutment (SCREW). At the screening visit, at crown insertion and at the 6-month follow-up, clinical parameters were measured at the implant and the contralateral tooth. Marginal bone levels, technical parameters, and esthetic outcomes were measured at the implants. At the 6-month follow-up, a microbiological test was performed and a soft tissue biopsy was harvested at the implants for histological analysis. Inflammatory cells and fibroblasts/-cytes were analyzed at the level of the sulcular epithelium, junctional epithelium, and connective tissue. The histological parameters were analyzed by means of a linear mixed model. RESULTS: Thirty-three patients completed the study, and implant and crown survival rates were 100% at 6 months. Histologically, the number of inflammatory cells tended to be higher in group CEM (p > 0.05). Moreover, significantly less inflammatory cells and fibroblasts/-cytes were found in the sulcular epithelium compared to the junctional epithelium and supracrestal connective tissue (p < 0.001). Four patients were tested positive for periodontal marker pathogens at the 6-month follow-up, and three of them belonged to group CEM. From crown insertion to the 6-month follow-up, median marginal bone levels changed only minimally and measured 0.31 and 0.32 mm in group CEM and 0.47 and 0.36 mm in group SCREW, respectively. Clinical and esthetic parameters remained stable over time and were comparable between natural teeth and implants as well as between the groups. CONCLUSIONS: Cemented reconstructions were associated with more inflammatory cells, and more patients were diagnosed with periodonto-pathogens. Both types of reconstructions resulted in similar radiological (marginal bone levels) and clinical outcomes (bleeding on probing and probing depth).